Thermal Biology Group, Exploratory Research Center on Life and Living Systems (ExCELLS), 5-1 Higashiyama, Myodaiji, Okazaki, Aichi, 444-8787, Japan.
Division of Cell Signaling, National Institute for Physiological Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi, 444-8787, Japan.
Commun Biol. 2023 Jan 23;6(1):88. doi: 10.1038/s42003-023-04482-1.
Transient receptor potential vanilloid 3 (TRPV3) belongs to the TRP ion channel super family and functions as a nonselective cation channel that is highly permeable to calcium. This channel is strongly expressed in skin keratinocytes and is involved in warmth sensation, itch, wound healing and secretion of several cytokines. Previous studies showed that anoctamin1 (ANO1), a calcium-activated chloride channel, was activated by calcium influx through TRPV1, TRPV4 or TRPA1 and that these channel interactions were important for TRP channel-mediated physiological functions. We found that ANO1 was expressed by normal human epidermal keratinocytes (NHEKs). We observed that ANO1 mediated currents upon TRPV3 activation of NHEKs and mouse skin keratinocytes. Using an in vitro wound-healing assay, we observed that either a TRPV3 blocker, an ANO1 blocker or low chloride medium inhibited cell migration and proliferation through p38 phosphorylation, leading to cell cycle arrest. These results indicated that chloride influx through ANO1 activity enhanced wound healing by keratinocytes.
瞬时受体电位香草酸受体 3(TRPV3)属于 TRP 离子通道超家族,作为一种非选择性阳离子通道,对钙具有高通透性。该通道在皮肤角质形成细胞中强烈表达,参与温热感觉、瘙痒、伤口愈合和几种细胞因子的分泌。先前的研究表明,钙激活氯离子通道 anoctamin1(ANO1)通过 TRPV1、TRPV4 或 TRPA1 的钙内流而被激活,这些通道相互作用对于 TRP 通道介导的生理功能很重要。我们发现,ANO1 由正常的人表皮角质形成细胞(NHEKs)表达。我们观察到,ANO1 在 NHEKs 和小鼠皮肤角质形成细胞中介导 TRPV3 激活时的电流。通过体外伤口愈合测定,我们观察到 TRPV3 阻断剂、ANO1 阻断剂或低氯介质通过 p38 磷酸化抑制细胞迁移和增殖,导致细胞周期停滞。这些结果表明,通过 ANO1 活性的氯离子内流增强了角质形成细胞的伤口愈合。